- Cyano-borrowing reaction: Nickel-catalyzed direct conversion of cyanohydrins and aldehydes/ketones to β-cyano ketone
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A direct nickel-catalyzed, high atom- and step-economical reaction of cyanohydrins with aldehydes or ketones via an unprecedented "cyano-borrowing reaction" has been developed. Cleavage of the C-CN bond of cyanohydrins followed by aldol condensation and conjugate addition of cyanide to α,β-unsaturated ketones proceeded to deliver a range of racemic β-cyano ketones with good to high yields. The practical procedure with the use of a commercial and less-toxic CN source bodes well for wide application of this protocol.
- Li, Zhao-Feng,Li, Qian,Ren, Li-Qing,Li, Qing-Hua,Peng, Yun-Gui,Liu, Tang-Lin
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p. 5787 - 5792
(2019/06/17)
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- Design, synthesis and investigation of new diphenyl substituted pyridazinone derivatives as both cholinesterase and Aβ-aggregation inhibitors
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Background: With respect to the increase in the average life expectancy, Alzheimer Disease (AD), the most common form of age-related dementia, has become a major threat to the population over the age of 65 during the past several decades. The majority of AD treatments are focused on cholinergic and amyloid hypotheses. Objective: In this study, three series of diphenyl-2-(2-(4-substitutedpiperazin-1-yl)ethyl)pyridazin- 3(2H)-one derivatives were designed, synthesized and investigated for their ability to inhibit both cholinesterase enzymes and amyloid-β aggregation. Method: The inhibitory activities of the synthesized compounds on AChE (from electric eel) and BChE (from equine serum) were determined by the modified Ellman’s method. The reported thioflavin T-based fluorometric assay was performed to investigate the effect of the selected compounds on the aggregation of Aβ1-42. The cytotoxic effect of the compounds (4g, 11g and 18g) was monitored in 3T3 cell lines to gain insight into therapeutic potential of the compounds by using MTT assay. The crystal structures of the AChE (1EVE) and BChE (1P0I) enzymes were retrieved from the RCSB Protein Data Bank and Molecular Operating Environment (MOE) software was used for molecular docking of the ligands. Results: Among the tested compounds, 5,6-diphenyl derivative 18g was identified as the most potent and selective AChE inhibitor (IC50 = 1.75 μM, Selectivity Index for AChE > 22.857). 4,6- Diphenyl derivative 11g showed the highest and the most selectivity for BChE (IC50= 4.97 μM, SI for AChE 0.124). Interestingly, 4,5-diphenyl derivative 4g presented dual cholinesterase inhibition (AChE IC50= 5.11 μM; BChE IC50= 14.16 μM, SI for AChE = 2.771). Conclusion: Based on biological activity results and low toxicity of the compounds, it can be said that diphenyl substituted pyridazinone core is a valuable scaffold. Especially, dual inhibitory potencies of 4,5-diphenylpyridazin-3(2H)-one core for the cholinesterase enzymes and Aβ- aggregation makes this core a promising disease-modifying agent.
- Kilic, Burcu,Erdogan, Merve,Gulcan, Hayrettin O.,Aksakal, Fatma,Oruklu, Nihan,Bagriacik, Emin U.,Dogruer, Deniz S.
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- Conjugate Hydrocyanation of Chalcone Derivatives Using Ethyl Cyanoacetate as an Organic Cyanide Source
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The conjugate hydrocyanation of chalcone derivatives using ethyl cyanoacetate as an organic cyanide source at room temperature under open air and transition metal-free conditions was described. The protocol has advantages of using relatively cheap, less toxic, stable and easy-to-handle cyanating reagent, high yield, and mild reaction condition.
- Li, Zheng,Yin, Junjun
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p. 1179 - 1184
(2017/07/24)
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- Tetraarylphosphonium inner-salts (TAPIS) as both Lewis base catalyst and phase tag
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Tetraarylphosphonium inner-salts (TAPIS) have been designed, synthesized and verified as recyclable and reusable Lewis base catalysts. The resulted TAPIS catalyst has been successfully applied in Michael addition, cyanation and trifluoromethylation reactions.
- Guo, Shuhui,Mi, Xueling
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supporting information
p. 2881 - 2884
(2017/07/11)
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- Functionalised diimidazolium salts: The anion effect on the catalytic ability
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The catalytic ability of some functionalised diimidazolium ionic liquids was tested using the Michael addition of malononitrile to t-chalcone as probe reaction. Diimidazolium salts characterized by the presence of 1-(1-imidazolylmethyl)-3,5-di-[1-(3-octylimidazolylmethyl)]benzene cation and differing in the anion structure were used. Both mono- and dianions were employed and among these some chiral anions generally used as organocatalysts were taken into account. Data collected were analysed both as function of ionic liquids structure and basicity, evaluated using the Hammett basicity function. Although the use of chiral anions did not allow performing a stereochemical control of the reaction, data collected demonstrate the high catalytic ability of the functionalised salts. Indeed, high conversions and yields were obtained under mild conditions and in significantly shorter reaction times with respect to the ones so far reported for this reaction.
- Rizzo, Carla,D'Anna, Francesca,Noto, Renato
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p. 58477 - 58484
(2016/07/07)
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- Enantioselective conjugate addition of cyanide to chalcones catalyzed by a magnesium-Py-BINMOL complex
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An enantioselective magnesium-catalyzed conjugate addition of trimethylsilyl cyanide to chalcones in the presence of Py-BINMOL with multiple stereogenic centers, through dual activation of substrates, has been successfully developed with moderate to good enantioselectivities and in good yields.
- Dong, Cheng,Song, Tao,Bai, Xing-Feng,Cui, Yu-Ming,Xu, Zheng,Xu, Li-Wen
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p. 4755 - 4759
(2015/10/05)
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- Thiourea-functionalized magnetic hydroxyapatite as a recyclable inorganic-organic hybrid nanocatalyst for conjugate hydrocyanation of chalcones with TMSCN
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The recoverable nanomagnetic catalyst was manufactured based on thiourea modified magnetic hydroxyapatite. Magnetic hydroxyapatite (mHAp) as the inorganic-organic hybrid support was fabricated using co-precipitate condition and then modified via the covalently anchoring of 1-(3,5-bis(trifluoromethyl)phenyl-3-propyl)thiourea. The hybrid nano-catalyst has been identified by TEM, SEM, FTIR, BET, TGA, and XRD. This nanocatalyst appeared efficient and robust in the 1,4-addition reaction of TMSCN to α,β-unsaturated aromatic enones in excellent yields (85-96%) under mild reaction condition and simple work-up process. This recoverable organocatalyst has a great potential as an industrially viable and eco-safe catalyst.
- Oskouie, Afsaneh Arefi,Taheri, Salman,Mamani, Leila,Heydari, Akbar
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- Synthesis of multisubstituted 1H-pyrrole: Selenium-catalyzed reaction of γ-nitro substituted carbonyl compounds and carbon monoxide
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The novel and efficient selenium-catalyzed reductive N-heterocyclization of γ-nitro substituted carbonyl compounds with carbon monoxide has been developed. Various multisubstituted 1H-pyrroles can be easily prepared by this protocol. The one-pot synthesis
- Umeda, Rui,Mashino, Tsukasa,Nishiyama, Yutaka
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p. 4395 - 4399
(2014/06/10)
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- Synthesis of β-cyanopropan-1-one derivates by domino reaction
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Domino nucleophilic addition was used for four-component Al 2O3-catalyzed environmentally friendly synthesis of polysubstituted β-cyanopropan-1-one. Domino nucleophilic addition involves removal of the cyano group linked to active methylene by the action of KF, and direct addition to enones. The reaction's capability for nucleophilic attack is F- > CN- in DMF. The use of low-toxicity reagents hints that the reaction is more environmentally friendly than traditional approaches. This journal is the Partner Organisations 2014.
- Dong, Hong-Ru,Dong, Wang-Jun,Li, Rong-Shan,Hu, Yi-Ming,Dong, Heng-Shan,Xie, Zhi-Xiang
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supporting information
p. 3454 - 3457
(2014/07/08)
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- Highly efficient asymmetric conjugate hydrocyanation of aromatic enones by an anionic chiral phosphate catalyst
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Chiral keto nitriles (β-cyano ketones) have been prepared by a facile and efficient asymmetric conjugate hydrocyanation of poorly active chalcone-type enones with benzophenone cyanohydrin. Using in situ generated 5-10 mol-% of sodium (S)-6,6′-di(1-adamantyl)-1,1′-binaphthyl-2,2′-diyl phosphate as catalyst and 5-10 mol-% of 2-tert-butylphenol as an additive, high yields and excellent enantioselectivities were obtained within 2 h in toluene at 80 °C. The development of catalysts, optimization of the reaction parameters, and substrate scope are reported. On the basis of the experimental results, HCN is shown to be the real cyanide source and a mechanism is proposed to explain the origin of the enantioselectivity with the chiral-anion-modified nucleophile HCN. The asymmetric conjugate hydrocyanation of poorly reactive chalcone-type enones with benzophenone cyanohydrin using an anionic chiral phosphate catalyst has been achieved in high yields (72-96 %) and excellent enantioselectivities (92-98 % ee). It is proposed that the chiral anion modifies HCN, the real nucleophile, in the transition state through hydrogen bonding. Copyright
- Wang, Yao-Feng,Zeng, Wei,Sohail, Muhammad,Guo, Jiyi,Wu, Shaoxiang,Chen, Fu-Xue
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p. 4624 - 4633
(2013/07/26)
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- Scandium(III) triflate catalyzed 1,4-addition of cyano group to enones using tetraethylammonium cyanide as the cyanide source
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A novel and practical method has been developed for the synthesis of β-cyanoketones using tetraethylammonium cyanide (Et4NCN, TEACN) / Sc(III) triflate and chalcones without the liberation of toxic HCN gas. Availability, safety, easy handling of the reagents, mild conditions of the reaction and high yields, make this method an attractive protocol for the direct synthesis of cyano substituted 1,4-adducts from enones.
- Ramesh, Samikannu,Lalitha, Appaswami
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p. 689 - 694
(2013/09/23)
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- Conjugate hydrocyanation of aromatic enones using potassium hexacyanoferrate(II) as an eco-friendly cyanide source
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A selective conjugate hydrocyanation of aromatic enones by a one-pot, two-step procedure using potassium hexacyanoferrate(II) as an original eco-friendly cyanide source, potassium hydroxide as a base, and benzoyl chloride as a promoter was described. This protocol has the advantages of a nontoxic cyanide source, high yield, and simple workup procedure. Georg Thieme Verlag Stuttgart · New York.
- Li, Zheng,Liu, Chenhui,Zhang, Yupeng,Li, Rongzhi,Ma, Ben,Yang, Jingya
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supporting information
p. 2567 - 2571
(2012/11/13)
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- Cyanation of α,β-unsaturated enones by malononitrile in open air under metal-catalyst-free conditions
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Cyanation of α,β-unsaturated enones by employing malononitrile as the organic cyanation source has been disclosed, which proceeds efficiently at room temperature in open air under metal-catalyst-free conditions. The Royal Society of Chemistry 2012.
- Lin, Shaoxia,Wei, Ying,Liang, Fushun
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p. 9879 - 9881
(2012/11/07)
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- Construction of 1,2,5-tricarbonyl compounds using methyl cyanoacetate as a glyoxylate anion synthon combined with copper(I) iodide-catalyzed aerobic oxidation
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A practical and efficient synthesis of various 1,2,5-tricarbonyl compounds is described. The synthesis has been carried out by a conjugate addition of methyl cyanoacetate to the β-position of α,β-unsaturated carbonyl compounds and a subsequent copper(I) iodide-catalyzed aerobic oxidation. In addition, various α-aryl- and α-alkyl-α-keto esters have been synthesized using a similar approach. Copyright
- Kim, Se Hee,Kim, Ko Hoon,Kim, Jae Nyoung
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supporting information; experimental part
p. 3335 - 3339
(2012/01/19)
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- Chiral sodium phosphate catalyzed enantioselective 1,4-addition of TMSCN to aromatic enones
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A facile enantioselective 1,4-addition of TMSCN to aromatic enones has been developed using chiral sodium phosphate. Thus, in the presence of 20 mol% of sodium salt generated in situ from (R)-3,3′-di(1-adamantyl)-1,1′- binaphthyl-2,2′-diylphosphoric acid and NaOH, β-cyano ketones were obtained in high yield (86-96%) and up to 72% ee within three hours at 80 °C in toluene.
- Yang, Jingya,Wu, Shaoxiang,Chen, Fu-Xue
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experimental part
p. 2725 - 2728
(2010/12/25)
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- Highly efficient Cs2CO3-catalyzed 1,4-addition of Me3SiCN to enones with water as the additive
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A facile and efficient 1,4-addition of Me3SiCN to enones has been achieved with perfect regioselectivity using Cs2CO3 as catalyst. Thus, with 0.5 mol% of Cs2CO3 and 4 equivalents of H2O as the additive excellent yields (81-99%) of -cyanoketones are obtained within one to five hours. Both aromatic and aliphatic enones are found suitable substrates for this protocol. Georg Thieme Verlag Stuttgart · New York.
- Yang, Jingya,Shen, Yongbin,Chen, Fu-Xue
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experimental part
p. 1325 - 1333
(2010/07/02)
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- Highly efficient syntheses of β-cyanoketones via conjugate addition of Me3SiCN to aromatic enones
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An efficient 1,4-addition of Me3SiCN to aromatic enones has been achieved with excellent yields (91%-99%) using CsF (1 mol%) as the catalyst and H2O (4 equiv.) as the additive in refluxing dioxane within 7 h. The perfect regioselecti
- Yang, Jingya,Chen, Fuxue
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experimental part
p. 981 - 987
(2010/10/03)
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- The highly efficient 1,4-addition of TMSCN to aromatic enones catalyzed by CsF with water as the additive
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An efficient 1,4-addition of TMSCN to aromatic enones has been achieved in excellent yields (91-99%) by CsF (1 mol%) as the catalyst and H2O (4 equiv) as the additive in refluxing dioxane within 2-7 hours. Georg Thieme Verlag Stuttgart - New Yo
- Yang, Jingya,Wang, Yinxian,Wu, Shaoxiang,Chen, Fu-Xue
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experimental part
p. 3365 - 3367
(2010/03/03)
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- An efficient conjugate hydrocyanation of chalcones and related enones with TMSCN under solvent- and additive-free microwave conditions
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A first example of solvent- and additive-free 1,4-addition reaction of α,β-unsaturated ketones such as chalcones, 3-nonen-2-one and benzalacetone with trimethylsilyl cyanide (TMSCN) is described. The addition of TMSCN to chalcones, 3-nonen-2-one, and benzalacetone under microwave irradiation in the absence of Lewis or Br?nsted acids and solvents, yielded the corresponding β-cyanoketones in good to moderate yields, as quite rapidly as in 5 min. No systematic substituent effect of chalcones on the yields was observed. No reaction of α,β-unsaturated esters such as methyl cinnamate with TMSCN took place under the same conditions.
- Iida, Hirokazu,Moromizato, Tatsuya,Hamana, Hiroshi,Matsumoto, Kiyoshi
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p. 2037 - 2039
(2007/10/03)
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- 3,4,6-Substituted pyridazines for treating neuropathic pain and associated syndromes
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The present invention is directed to the use of 3,4,6-substituted pyridazines such as those characterized by structure I for treating conditions such as neuropathic pain among others.
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Page/Page column 17
(2008/06/13)
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- THERAPEUTIC AGENT FOR DIABETES
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A therapeutic agent for diabetes, which comprises a compound of the formula [I] wherein Xis a group of the formula wherein R4and R5are the same or different and each is a hydrogen atom, an optionally substituted alkyl having 1 to 5 carbon atoms and the like, and R6is a hydrogen atom or an amino-protecting group; R1is an optionally substituted alkyl having 1 to 5 carbon atoms, an optionally substituted alkenyl having 2 to 6 carbon atoms and the like, R2is a hydrogen atom, an optionally substituted alkyl having 1 to 5 carbon atoms and the like, R2' is a hydrogen atom, and R3is an optionally substituted alkyl having 1 to 5 carbon atoms and the like, a prodrug thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof and a solvate thereof. The compound of the present invention shows superior blood sugar decreasing action on the state of hyperglycemia, but does not affect the blood sugar when it is in the normal range or in the hypoglycemic state, which means that it is free of serious side effects such as hypoglycemia. Therefore, the compound of the present invention is useful as a therapeutic drug for diabetes and also useful as a preventive of the chronic complications of diabetes.
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- Formaldehyde dialkylhydrazones as neutral formyl anion and cyanide equivalents: Nucleophilic addition to conjugated enones
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A versatile methodology for the nucleophihc formylation and cyanation of conjugated enones is reported. The procedure is based on the use of formaldehyde dimethylhydrazone, which, acting as a neutral formyl anion equivalent, adds to preformed trialkylsilyl-enone complexes. Both 4-(silyl- oxy)-3-enal hydrazones 3 or deprotected 4-oxo aldehyde monohydrazones 4 can be obtained at products depending on quenching conditions. In full analogy, an asymmetric version of the reaction using chiral formaldehyde SAMP- hydrazone as a neutral synthon of the chiral formyl anion has been developed, giving rise to the corresponding adducts 5 and 6 in good yields and with excellent diastereoselectivities (de 85-≤98%). Ozonolysis or HCl-mediated hydrolysis of adducts 4 and 6 readily affords racemic and optically enriched 4-oxo aldehydes 7, respectively. Additionally, high-yielding MMPP-oxidative cleavage of 4-oxo hydrazones 4 and 6 has been performed to obtain 4-oxo nitriles 8 in racemic and optically enriched forms, respectively. In this way, interesting chiral bifunctional building blocks, some of them bearing newly created stereogenic quaternary centers, have been efficiently synthesized.
- Diez,Fernandez,Gasch,Lassaletta,Llera,Martin-Zamora,Vazquez
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p. 5144 - 5155
(2007/10/03)
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- A new conversion of primary nitro compounds into nitriles
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The reaction of primary nitro compounds with isocyanides and isocyanates in the presence of a base leads to a new preparation of nitriles. The reaction probably proceeds through the in situ formation of a nitrile oxide followed by a fast oxygen transfer with the isocyanide. Combined with the Knovenagel addition of nitromethane to cyclic ketone, this reaction brings a highly effective regioselective formation of cyclic α-β unsaturated nitriles.
- El Kaim, Laurent,Gacon, Ariane
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p. 3391 - 3394
(2007/10/03)
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- Reactions of 2-(Dialkylamino)arylacetonitriles with Acetylenes Under Basic Conditions. A Simple Synthesis of Substituted Mono and Diketones
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2-(Dialkylamino)arylacetonitriles 1 react with acetylenes 2a,b in dimethyl sulfoxide, powdered sodium hydroxide and triethylbenzylammonium chloride as a catalyst to give 3 and/or 4.The latter are formed via addition of anion 8 to immonium salt 9.The type of product formed depends on the basicity of amino moiety in 3.Furthermore, compound 1 adds to C-1 of acetylene 2c affording the vinyl derivatives 15.The products 3,4,11 and 15 are hydrolyzed to give ketones 5-7,12 and 16, respectively.
- Zdrojewski, T.,Jonczyk, A.
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p. 224 - 233
(2007/10/02)
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- Enanthioselective Phase-Transfer Catalysis by Optically Active Crown Ethers
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1,2-Bis(hydroxymethyl)-15-crown-5 (1a), its dibenzyl ether (1b), and a series of esters with substituted benzoic acid (3) were probed as enanthioselective phase-transfer catalysts.Optical yields were observed in epoxidations of unsaturated ketones by hypochlorite and in cyanide additions to such compounds.The maximum ee value was 45percent.Polar side groups of the optically active crown ethers proved to be vital for enanthiomeric excesses.
- Dehmlow, Eckehard V.,Sauerbier, Christiane
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p. 181 - 186
(2007/10/02)
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- Synthesis of Heterocyclic Compounds, XXXVIII. - Five-membered Heterocycles by Cyclization of 3-Benzoyl-4-oxobutanenitriles
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A synthesis of N-benzylidene-2-furanamines 8 by means of cyanide addition to acylchalcones 2, followed by piperidine-catalyzed cyclization in the presence of an aldehyde is reported.The 2-pyrrolones 4 are formed together with the compounds 8.In the absence of an aldehyde no furan is obtained.The intermediate 2-aryl-3-benzoyl-4-oxo-4-phenylbutanenitriles 3are easily isolated.The N-benzylidene-2-furanamines 9 are obtained from the oxonitriles 5.
- Ciller, J. A.,Seoane, C.,Soto, J.L.
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- Asymmetric Induction in the Michael Reaction by Means of Chiral Phase-transfer Catalysts derived from Cinchona and Ephedra Alkaloids
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Asymmetric induction in the Michael reaction has been achieved using alkaloidonium salts in a two-phase system with optical yields of up to 36 and 26percent in the addition to αβ-unsaturated ketones of thiols and nitroalkanes respectively.The presence of a hydroxy-group β to the 'onium function is essential to achieve substantial asymmetric syntheses.
- Colonna, Stefano,Re, Alberto,Wynberg, Hans
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p. 547 - 552
(2007/10/02)
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